Scientists improve anti-tumor power of CAR-T cells | Hacker News Reader

Scientists improve anti-tumor power of CAR-T cells

insideprecisionmedicine.com

108 pointsbirriel43 comments

They used DCA (dichloroacetate) to do the inhibition. It's going to be ironic, if DCA will actually be useful for cancer treatment.

For those who don't know, DCA treatment made a lot of noise in the early 2000-s, with all kinds of conspiracy theories about it. Like drug companies covering it up because it "can't be patented". People even crowd-funded its clinical trials.

Unfortunately, it turned out to be too toxic on its own because cancer cells can adapt to the levels of DCA that kill the rest of the patient.

I'm 31 which means I got maybe around 20? years before I become a prime target of potential cancers. I really hope by then most of even today's abilities are at least available in most hospitals, since right now cancer treatment in Estonia is still old-school chemotherapy. Not even sure if our doctors have heard of Car-T. 20 years is probably too little time to make dying from cancer a thing of the past, but maybe getting today's cutting edge mainstream by then would be possible.

Immunotherapy is the direction we want to go, but Car-T therapy can kill the patient.

Old school chemotherapy still works as a first-line defense, and the newer stuff is getting better (paclitaxel, antibody drug conjugates (ADC)).

Looking at major developments in the world I feel like we're moving away from societies that enable the best healthcare for as many as possible and rather move to nationalistic, authoritarian states that drag everybody back into a 20th century mindset. Money spent on defence won't be spent on research and sure as hell not on affordable healthcare. The tech might be there when you hit 50 but will you be able to afford it?

Yeah, I tend to agree. Next year I'm moving away from Estonia, to Finland, precisely because at least there the government still cares to a point about healthcare whereas here they have entirely given up, defund it on a regular basis, and gatekeep access to specialists via family doctors who don't allow you to go anywhere and instead of any tests give you pills. All sorts of pills. Knee pain? Antidepressants on a Tuesday, ibuprofen on a Wednesday. People don't get help, just suppressing of symptoms (in the best case) and told to go die somewhere (in the worst case).

And that would be fine and all, and I wouldn't even care, if I didn't have to pay half my salary to taxes. If I could choose to not pay healthcare tax, I could use that money to get a very, very nice private healthcare insurance instead. But I'm not allowed to choose here.

I dream of future where cancer of every kind is a fully treatable malady at best, or manageable chronic condition at worst.

We are not there yet, but I have a hope that we are no further than century away from achieving that.

If we can avoid destroying ourselves, we will achieve it.

Maybe the notion that we can live for an extended period of time will motivate more people to become ecologically responsible.

Our hearts would eventually give out anyway. I'd just much rather die of a sudden heart attack than a long and torturous cancer battle.

> Our hearts would eventually give out anyway.

We need to fix that too.

At some point, it is good to die, to make room for the next generation, no matter how great you are. Others deserve a shot, too.

No. Nothing is worth the utter destruction of a person. People have an endless capacity to learn and grow, and there is no limited room for people that's getting used up; the universe is a very big place. Longevity will certainly lead to some interesting challenges; bring them on, they're worth solving and none of them are worth killing people to avoid. And preventing people from living is absolutely equivalent to killing them.

Personally, for me I'd say "no". But I decided not to have kids, and I don't think you can have unlimited reproduction and immortality. It would be interesting to give people the choice between eternal life and kids. Like in the Highlander, your "prize" for having kids is mortality.

I wish.

There was another news bit recently re: polyethylene glycol, to reduce the damage done to healthy cells.

https://penntoday.upenn.edu/news/suit-armor-cancer-fighting-...

We should mimic the elephant - they have 20 variations of p53 gene in their DNA - bigger body mass and similiar lifespan but more cells but they don't get cancer.

Study after study after study says diet and lifestyle are major factors in every deadly disease. But it's not socially acceptable to suggest that as an approach.

However, having already committed the unspeakable sin and egregious faux pas, I will suggest that if cancer is a thing you fret about, you can do something to reduce your risk starting today.

ill never eat PFAS again

Good for you. Want to share any good websites you have for how to support your goal here?

If I'm eating PFAS, I'd like to know.

PFAS (aka "forever chemicals") are present in everything including drinking water and breast milk so yes, you are eating PFAS.

Diet and exercise are near-universally accepted as reasonable health advice and is basically ubiquitous.

I'm aware of that.

It doesn't matter. You can't have a meaty discussion about this in relation to actually trying in earnest to avoid or delay cancer.

For the record, this was posted as a PSA without replying to any of the comments that made me think people could use a reminder because a direct reply gets interpreted as a personal attack.

What “this” are you talking about?

I mean, I do, and people should but there’s no denying there’s still a huge element of chance though. Plenty of people have fantastic diet and exercise a lot and still get cancer… And environmental effects that may be outside people’s control. Anyone might have already been exposed with absolutely no knowledge to, say, asbestos fibres that will give them mesothelioma in another 20 years. And there’s no way (currently known) to stop it even if they did know they’d been exposed.

Yeah, there's a lot of variables. So no point in even trying. Amirite?

Plenty of “healthy” people die of cancer. My sister in law passed away at 49. She had no family history of cancer, ate healthy, ran daily, was not overweight for her entire life.

I do have a family history of cancer.

My mother, sister, brother, father, multiple aunts and grandmother have had it one or more times.

I've had it zero times.

That’s called luck. Babies don’t get leukemia because they lack diet and exercise.

Good diet and exercise can lower your risk. They cannot eliminate risk. You can do everything right and still get cancer.

Thus diet and exercise are also not reasonable substitutes for researching better treatments for those who do get cancer.

I don't think diet and exercise are the full story. My initial comment says diet and lifestyle, not diet and exercise.

I'm trying to step away from this discussion. It is kind of off topic and I don't think it's productive.

This is an obnoxious response that has no bearing on the content of the article. You may as well state that cancer is caused by not praying to the god of your choice or by not following some specific 12-step program that you have deemed vital.

There is no truth to your statement that is it not socially acceptable to suggest diet and lifestyle changes to improve quality of life. Those suggestions are made all the time and people who suggest them in general suffer little to no negative consequences. I am not sure how you go about making those suggestions, but perhaps your approach is less optimal. There are situations where suggestions will be made and go unheeded. Many alcoholics know that drinking is bad for them and many smokers know that smoking is not having a positive effect on their health. They choose to ignore the advice.

My wife, who passed away almost two years ago, received CAR-T therapy for triple-hit large B-cell lymphoma. I can assure you that her diet and lifestyle choices were most likely not the cause. CAR-T therapy is not made available to any and all and her case was most likely caused by exposure to specific toxic chemicals. I only wish she would have survived the extremely toxic and negative side-effects of the therapy so she could be here to reply to your comment.

I'm very sorry for the passing of your wife.

> There is no truth to your statement that is it not socially acceptable to suggest diet and lifestyle changes to improve quality of life.

And yet DoreenMichele is voted down, and you angrily argued that her statement is no more scientifically valid than a religion.

It sure looks like it's not socially acceptable to you, at least.

Diet and exercise are universally failed interventions to stop major diseases (CVD, cancer...). People who have a vested interest in them promote them (e.g. exercise specialists, keto experts, vegan gurus, your favorite TV Dr, harvard nutrition dept whose livelihood depends on the effectiveness of "optimal diet" etc), but the results in intervention trials have been extremely disappointing.

1) The best diet studies where people were asked to follow Mediterranean diet only managed to lower CVD and/or mortality by 10s of % points. This is a very poor outcome. At best adds a few years to someone's lifespan. At best. The average Mediterranean dieter fares a lot worse. https://pubmed.ncbi.nlm.nih.gov/26528631/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368053 Don't get me started about Keto, Vegan etc. Those have even less convincing evidence regarding hard outcomes (e.g. MACE, Cancer etc) though our opinion might change if they ever get tested in large scale.

2) Exercise is even worse. It has virtually zero effect on CVD outcomes, mortality outcomes in trials where participants were asked to change their behaviors. "Exercise did not reduce all-cause mortality and incident CVD in older adults or in people with chronic conditions, based on RCTs comprising ∼50,000 participants" https://scholar.google.com/scholar?cluster=10512580439138189...

It's a myth that diet and exercise will save you from Cancer or CVD. There's virtually zero evidence for that, when you look at things from intervention point of view -- intervention evidence is the only evidence acceptable in science. The rest is pseudo-science or proto-science.

Btw, I believe weight loss is the best thing you can do to live longer (that is if you're overweight or obese). But diets still universally fail. E.g. bariatric surgery probably works, maybe drugs will be shown to work (Tirzepatide/Semaglutide I'm looking at you). A publication on how 90% of obese dieters fail after 1-2 yrs on the same diet: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764193/

> Exercise is even worse. It has virtually zero effect on CVD outcomes, mortality outcomes in trials where participants were asked to change their behaviors.

This is simply not true and you jump through some curious hoops to make it look credible. The paragraph you cite basically says "if you start after 60 it's too late". Is then proceeds to add that a few weeks of exercise are not enough, and a few months of follow-up don't catch measurable differences.

But if you actually read the full study that you cite and check the papers it reviews, you'll see that multi-year interventions at middle age with multi-year follow-ups are extremely effective.

Here's one of the reviewed papers, with 6-year intervention and 30-year follow-up: https://www.thelancet.com/journals/landia/article/PIIS2213-8...

> During the 30-year follow-up, compared with control, the combined intervention group had a median delay in diabetes onset of 3·96 years (95% CI 1·25 to 6·67; p=0·0042), fewer cardiovascular disease events (hazard ratio 0·74, 95% CI 0·59–0·92; p=0·0060), a lower incidence of microvascular complications (0·65, 0·45–0·95; p=0·025), fewer cardiovascular disease deaths (0·67, 0·48–0·94; p=0·022), fewer all-cause deaths (0·74, 0·61–0·89; p=0·0015), and an average increase in life expectancy of 1·44 years (95% CI 0·20–2·68; p=0·023).

Healthcare Triage: "To the research!"

https://www.youtube.com/watch?v=hkO44tzkXyQ

https://www.youtube.com/watch?v=SFBBjynBpSw

tl;dw -- the relative risk reduction can be as high as 50%, and depending on risk factors, the absolute risk reduction can be 5%.

This is biased reading at its worst. I was simply stating what the authors concluded based on their analysis of 10-20 studies (not just one). This is what they say in the abstract: "The results show that exercise does not reduce all-cause mortality and incident CVD in older adults or in people with chronic conditions, based on RCTs comprising ∼50,000 participants."

One study with 500 people doesn't prove a point.

Of the top of my head I know at least one other study where mid-life lifestyle intervention didn't reduce mortality (it slightly increased it in a statistically non-significant manner). 21 yrs follow up. ~3000 people. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.0...

Diets don’t fail, people fail to follow diets. Which is probably fine in the long run, because they’re always there for people who want them. There’s probably never going to be a wonder drug for obesity though. But Anavar or Trenbolone would work better than Semaglutide, and the side effects likely aren’t that much worse (all of those options are still bad ideas).

> Diets don’t fail, people fail to follow diets.

That's like saying, "Exhortations to developers not to write bugs don't fail, programmers fail to follow exhortations." Guess what? Even the most skilled and well-intentioned programmers will write bugs, despite their best efforts; and lots of programmers simply won't put out their best efforts. If your goal is simply to find someone to blame, then sure, blame the developers. But if your goal is better software, exhortations not to write bugs are simply an ineffective intervention. You need to introduce other measures, like type systems, linters, static checkers, code reviews, and testing.

Similarly, if people consistently fail to follow diets, then the current crop of diets are an ineffective intervention. If your goal is to assign blame, then sure, you can stop there and feel good that you've found someone to blame. But if your goal is to actually make the situation better, then you need to find something else.

> That's like saying, "Exhortations to developers not to write bugs don't fail, programmers fail to follow exhortations."

It’s not even the littlest bit like that. Nobody knows how to write software without bugs. Everybody knows how to lose weight. Just do some exercise and eat less calories than you burn. You don’t even have to do the exercise part, but you should do at least a little bit if you’re trying to be healthy. The only problem is that most people don’t want to commit the effort or make the sacrifices required to do that. If anybody’s trying to find something to blame, it’s the legions of obese people desperately in search of any reason for their obesity other than their own lifestyle choices. It’s a lifestyle problem, and it’s unlikely that there will ever be a pharmaceutical intervention for it that doesn’t have pretty bad side effects. But if bad side effects are acceptable for you, then magic drugs already exist for obesity. Anabolic steroids. They’ll do exactly what you’re looking for.

> But diets still universally fail. E.g. bariatric surgery probably works, maybe drugs will be shown to work (Tirzepatide/Semaglutide I'm looking at you). A publication on how 90% of obese dieters fail after 1-2 yrs on the same diet:

This is not evidence that diets universally fail.

>> Study after study after study says diet and lifestyle are major factors in every deadly disease. But it's not socially acceptable to suggest that as an approach.

This is too simple of an statement for such a complex disease, so is therefore, misleading.

If we want more substantial studies, we turn to the UK, because they have a unified health system and have a massive collection of data on the general population. Timothy Key, et. al., Oxford, wrote a great summary of attributable factors (albeit a secondary data analysis). Outside of obvious factors such as smoking, alcohol, and obesity, what you put into your body becomes less and less a probability of being a cancer factor compared to age and genetics.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190379/

>> Early case-control studies indicated that higher intakes of fruit and vegetables were associated with a lower risk of several types of cancer. But subsequent prospective studies, which are not affected by recall or selection bias, produced much weaker findings. In the 2018 World Cancer Research Fund report neither fruits nor vegetables were considered to be convincingly or probably associated with the risk of any cancer. There was suggestive evidence for protection of some cancers, and risk might increase at very low intakes. Specific components of certain fruits and vegetables might have a protective action.

>> Vegetarians eat no meat or fish and usually eat more fruit and vegetables than comparable non-vegetarians. The risk of all cancer sites combined might be slightly lower in vegetarians and vegans than in non-vegetarians, but findings for individual cancers are inconclusive.

> Outside of obvious factors

Rephrased, if you exclude all the obvious ways in which DoreenMichele's statement is true, then you're left with the ways it's not true alongside the ways it's true but not obviously so.

This is an argument anyone will grant, but it's a tautology that doesn't tell us much of use.

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